Compartmentalized immune response in leishmaniasis

Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of inform...

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Detalhes bibliográficos
Autores: Rodriguez-Cortes, Alheli|||0000-0003-3617-0119, Carrillo, Eugenia, Martorell, Susanna, Todolí, Felicitat, Ojeda García, Ana, Martínez-Flórez, Alba, Urniza, Alicia, Moreno, Javier, Alberola, Jordi|||0000-0002-1033-6339
Formato: artículo
Fecha de publicación:2016
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:215950
Acesso em linha:https://ddd.uab.cat/record/215950
https://dx.doi.org/urn:doi:10.1371/journal.pone.0155224
Access Level:acceso abierto
Palavra-chave:Animals
Antibodies, Protozoan
Biomarkers
Bone Marrow
Cytokines
Dogs
Female
Leishmania infantum
Leishmaniasis, Visceral
Liver
Lymph Nodes
Organ Specificity
Parasites
Real-Time Polymerase Chain Reaction
Skin
Descrição
Resumo:Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-β cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an antiinflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease.